Cellular development occurs as a series of chemical events. Basic questions concerning mechanisms of control of various steps in the developmental process remain to be answered. Differentiation is undoubtedly dependent on proper functioning of control systems responsible for selection of the unique order of new metabolic processes. Abnormal differentiation, e.g. neoplasia, would be expected if such controls were not properly exerted. Understanding defects in differentiation, such as malignancy, will depend on a foundation of knowledge of the events and mechanisms concerned with normal differentiation. Biosynthesis of the proteins directly involved in translation, i.e. ribosomal, transfer, initiation, and termination factors, clearly must be linked to other developmental events by as yet undetermined control systems. Synthesis of these elements must occur during or as a result of mitosis in order to satisfy the requirements of the two daughter cells. Also during differentiation new classes of ribosomal proteins or initiation factors may be required for synthesis of new classes of metabolic enzymes. The objectives of this research program are twofold: 1) to determine the genetic loci containing information for proteins of the translation apparatus. 2) to determine the genetic mechanisms involved in control of the expression of these genes. Genetic loci for elements of the protein synthetic apparatus of yeast will be determined by mutational events conferring resistance of specific elements to inhibitors of protein synthesis. Having collected a number of markers for several proteins, control mutations will be selected for which affect expression of known structural genes. Success of this approach will provide knowledge of genetic mechanisms of control of macromolecular synthesis. It is anticipated that such knowledge is essential to an understanding of the normal events involved in growth and differentiation. Understanding the normal events of these processes will provide a basis for understanding deviations leading to the neoplastic state.